Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0344307 (analgesia)
 28,200 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nociceptin/orphanin FQ (nociceptin/OFQ), a newly discovered heptadecapeptide has been regarded as an endogenous ligand for orphan opioid receptor. The present study was designed to investigate the effect of nociceptin/OFQ on pain response and opioid analgesia in the rat formalin test. The results showed that intracerebroventricular injection of 1 microg nociceptin/OFQ enhanced the pain response, and 0.1 or 0.5 microg nociceptin/OFQ had no effect on formalin-induced pain. When 0.1 or 1 microg nociceptin/OFQ were used together with mu-, delta-, or kappa-opioid receptor agonists, endomorphin-1, DSLET or U50488H, respectively, it attenuated mu- and kappa- but not delta-receptor mediated analgesia. On the other hand, intrathecal injection of nociceptin/OFQ (0.1, 1 and 5 microg) reduced the pain response in the formalin test. In conclusion, nociceptin/OFQ potentiated formalin-induced pain response and antagonized opioid analgesia in the rat brain but inhibited pain response in the spinal cord.
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PMID:Distinct effect of intracerebroventricular and intrathecal injections of nociceptin/orphanin FQ in the rat formalin test. 1010 Sep 30

Nocistatin is a recently characterized neuropeptide derived from the preprohormone containing nociceptin (Orphanin FQ, OFQ). Nocistatin was reported to antagonize OFQ induced allodynia, hyperalgesia and prostaglandin E2-elicited pain responses. The aim of the present study was to determine whether nocistatin, injected intracerebroventricularly (i.c.v.), would reverse the anti-morphine effect of OFQ in rats using the tail-flick latency (TFL) as the nociceptive index. I.c.v. injection of nocistatin at doses of 0.005, 0.05, 0.5, 5, 50, and 500 ng produced no significant changes in the basal TFL, nor did it affect morphine analgesia. However, it significantly reversed the antagonistic effect of OFQ on morphine analgesia when co-injected i.c.v. at doses of 0.05, 0.5, 5, 50 and 500 ng per rat with OFQ. The dose-response curve was bell-shaped and the most effective dose was 0.5 ng. The results suggest that nocistatin can reverse the anti-morphine effect of OFQ in rat brain.
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PMID:Nocistatin reverses the effect of orphanin FQ/nociceptin in antagonizing morphine analgesia. 1020 25

Recently, opioid receptor like1 (ORL1) receptor was identified. The ORL1 receptor is a G protein coupled receptor and the sequence of the ORL1 receptor is closely related to that of the opioid receptors. Nociceptin/orphanin FQ has been identified as a potent endogenous agonist of the ORL1 receptor and the sequence of nociceptin/orphanin FQ is closely related to that of dynorphin A. Nociceptin/orphanin FQis not active at the classical opioid receptors, such as mu, kappa and delta receptors. The distribution of prepronociceptin mRNA is distinct from that of the opioid peptide precursor. Mice lacking the ORL1 receptor showed no significant differences in nociceptive threshold compared with wild mice. The role of nociceptin/orphanin FQ on nociceptive transmission is unclear. Intracerebroventricular (i.c.v.) injection of nociceptin/orphanin FQ produced hyperalgesia and allodynia and antagonized morphine analgesia. On the other hand, intrathecal injection of low dose nociceptin/orphanin FQ produces allodynia, but high dose of nociceptin/orphanin FQ produces an analgesic effect. Although we do not fully understand the mechanisms that produce the difference between the effect of i.c.v. injection of nociceptin/orphanin FQ and that of intrathecal injection of nociceptin/orphanin FQ, we believe that spinal ORL1 receptor may be the next receptor which should be targeted by drugs designed for the treatment of pain.
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PMID:Nociceptin/orphanin FQ: role in nociceptive information processing. 1021

Orphanin FQ has been shown to possess anti-opioid activity at supraspinal level. Our previous work revealed that chronic morphine tolerance could be reversed by intracerebroventricular (i.c.v.) injection of OFQ IgG to rats. In this study, we used radioimmunoassay (RIA) to assess the changes of Orphanin FQ immunoreactivity (OFQ-ir) in cerebroventricular perfusate, periaqueductal gray (PAG) and amygdala of rats made tolerance to morphine (10-60 mg/kg, s.c., t.i.d., for 5 days). The results indicated that: (1) In rats administrated with morphine for 3 and 5 days, the content of OFQ-ir in cerebroventricular perfusate increased by 25% and 52% over the NS control group. (2) The content of OFQ-ir in PAG of rats receiving 1d, 3d and 5d injections of morphine showed an increase of 17%, 48% and 81% respectively over NS group. (3) The content of OFQ-ir in amygdala of rats given 3d and 5d of morphine showed a 36% and 55% increase compared with corresponding control group. It is suggested that continuous use of high doses of morphine accelerated the release and biosynthesis of OFQ in rat brain to antagonize the effect of opioids, which may play a role in the development of morphine tolerance, and that brain OFQ may serve as a delayed negative feedback control on opioid analgesia.
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PMID:Accelerated release and production of orphanin FQ in brain of chronic morphine tolerant rats. 1022 16

Orphanin FQ/Nociceptin (OFQ/N) administered peripherally was an effective analgesic in the tailflick test in mice (ED50 16.3 microg). It had a peak effect at 5 min and lasted up to 30 min. The kappa3 analgesic naloxone benzoylhydrazone was also active peripherally (ED50 3.8 microg). The analgesic actions of both agents were blocked by naloxone. Neither OFQ/N(1-11) nor OFQ/N(1-7) had appreciable peripheral activity. Antisense mapping both compounds against the murine orphan opioid receptor (KOR-3) confirmed the importance of this clone in their actions. Antisense probes targeting the second and third coding exons significantly lowered the analgesic effects of both compounds. However, the antisense targeting the first coding exon blocked only the actions of OFQ/N and not kappa3 analgesia.
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PMID:Peripheral orphanin FQ/nociceptin analgesia in the mouse. 1037 27

Orphanin FQ (also known as nociceptin) is a 17-amino-acid peptide which acts as a potent endogenous agonist of the orphan opioid receptor-like (ORL1) receptor. Endomorphin-1, a 4-amino-acid peptide discovered recently, is a potent and selective endogenous agonist for the mu-opiate receptor. In the present study, the effect of OFQ or/and endomorphin-1 on the response to noxious thermal stimuli was observed using the tail-flick test in rats. Intracerebroventricular (i.c.v.) administration of OFQ (1, 5 microg) could shorten tail-flick latency; In contrast, intrathecal (i.t.) administration of OFQ (1, 2 or 10 microg) could increase the latency; i.c.v. (1, 2, 5 microg) or i.t. (0.2, 2, 5 microg) administration of endomorphin-1 dose-dependently increased the latency, indicating an analgesic effect. Furthermore, OFQ (0.1-5 microg) when intraventricularly injected together with endomorphin-1 (5 microg), could dose-dependently reverse the analgesia induced by the latter. On the contrary, OFQ (1 microg) intrathecally injected together with endomorphin-1 (0.2 microg) could further increase the tail-flick latency. The results showed that OFQ at the supraspinal level produces hyperalgesia and is antagonistic to endomorphin-1, while at the spinal level it produces analgesia and is synergic with endomorphin-1. Different interaction mechanism between OFQ and endomorphin-1 in the brain and the spinal cord is thus suggested.
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PMID:Effects of orphanin FQ on endomorphin-1 induced analgesia. 1041 79

The neuropeptide orphanin FQ (also known as nociceptin; OFQ/N) has been implicated in modulating stress-related behavior. OFQ/N was demonstrated to reverse stress-induced analgesia and possess anxiolytic-like activity after central administration. To further study physiological functions of OFQ/N, we have generated OFQ/N-deficient mice by targeted disruption of the OFQ/N gene. Homozygous mice display increased anxiety-like behavior when exposed to a novel and threatening environment. OFQ/N-null mice show elevated basal pain threshold but develop normal stress-induced analgesia. Interestingly, these mice show impaired adaptation to repeated stress when compared with wild-type mice, whereas their performance in spatial learning remained unaffected. Basal and poststress plasma corticosterone levels were found to be elevated in OFQ/N-deficient animals. Thus, OFQ/N appears to be crucially involved in the neurobiological regulation of stress-coping behavior and fear.
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PMID:Targeted disruption of the orphanin FQ/nociceptin gene increases stress susceptibility and impairs stress adaptation in mice. 1046 28

1. [Phe1psi(CH2-NH)Gly2]nociceptin-(1 - 13)-NH2 (Phepsi), a tridecapeptide analogue of orphanin FQ/nociceptin (OFQ/N), was introduced as a competitive antagonist of opioid receptor-like orphan receptor (ORL1) in guinea-pig ileum and mouse vas deferens preparations in vitro but was recently found to act as an agonist in vivo. 2. In the periaqueductal gray, a site enriched with both OFQ/N and ORL1 and involved in OFQ/N-induced hyperalgesia and anti-analgesia, the effects of Phepsi and OFQ/N on the membrane current were studied using whole cell patch clamp recording technique in rat brain slices. 3. OFQ/N (0.01 - 1 microM) activated an inwardly rectifying type of K+ channels in ventrolateral neurons of PAG. Phepsi (0.03 - 1 microM), like OFQ/N, also activated this inward rectifier but had only 30% efficacy of OFQ/N. 4 At maximal effective concentration (1 microM), Phepsi reversed the increment of K+ conductance induced by OFQ/N (300 nM) by 46%. On the other hand, Phepsi also prevented the effect of OFQ/N if pretreated before OFQ/N. 5 It is suggested that Phepsi acts as a partial agonist of ORL1 that mediates the activation of inwardly rectifying K+ channels in ventrolateral neurons of rat periaqueductal gray.
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PMID:[Phe1psi(CH2-NH)Gly2]nociceptin-(1 - 13)-NH2 activation of an inward rectifier as a partial agonist of ORL1 receptors in rat periaqueductal gray. 1049 40

Nociceptin and its N-terminal fragment, nociceptin (1 7), were administered intrathecally (i.t.) into conscious mice. Nociceptin (3.0 fmol) produced a significant reduction in the nociceptive thermal threshold (hyperalgesia) measured as the tail-flick and paw-withdrawal responses. Nociceptin (1-7), injected i.t., at 150-1200 fmol had no significant effect. However, when nociceptin (1-7) (150 1200 fmol) was injected simultaneously with nociceptin (3.0 fmol), nociceptin-induced hyperalgesia was significantly reduced. Analgesia induced by a high dose (1200 pmol) of nociceptin was not antagonized by co-administration of nociceptin (1-7) (1200 fmol). These results suggest that N-terminal fragments of nociceptin formed endogenously could modulate the hyperalgesic action of nociceptin in the spinal cord.
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PMID:Nociceptin (1 - 7) antagonizes nociceptin-induced hyperalgesia in mice. 1055 29

The recently discovered peptide nociceptin/orphanin FQ (N/OFQ) and its receptor NOR share many structural similarities with the opioid peptides and their receptors. The anatomical distributions of N/OFQ and NOR are similar to those of opioid peptides and receptors. In addition, NOR and opiate receptors couple via the same G-proteins to similar effectors, such as Ca(2+) channels, K(+) channels, adenylyl cyclase, and several protein kinases. Thus, the behavioral effects of N/OFQ have been investigated in the context of known opiate effects, and a possible connection has been sought between the effects of these two homologous signaling systems. Originally characterized as a nociception-producing peptide, N/OFQ has now been shown to have diverse effects on nociception, as well as effects on many other behaviors. With regard to nociception, the peptide has been reported to produce hyperalgesia, reversal of opioid-mediated analgesia, analgesia, and allodynia. N/OFQ also has effects on other behaviors, such as locomotion, feeding, anxiety, spatial attention, reproductive behaviors, and opiate tolerance. The relationship between opiates and N/OFQ is strengthened by the fact that opiates also affect these behaviors. However, the exact nature of the relationship of N/OFQ with opiates-opiate-like versus antiopiate-remains controversial. This review will detail the diverse effects of N/OFQ and suggest that this peptide, like other putative antiopiate peptides, can be described as 'opiate modulating. '
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PMID:Opiate modulating properties of nociceptin/orphanin FQ. 1070 32


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